ProjectAbstract Biological networks organize specific chemical reactions in space and time. In cell signaling, scaffold proteins coordinate the formation of physical complexes that link multiple signaling proteinstogether.Thesescaffoldproteinshavemanyfunctionalroles:theycanrecruitproteinsto particular subcellular locations, serve as platforms to recruit regulatory factors, and direct pathwaystospecificoutputs.Scaffoldproteinsarealsothoughttoacceleratespecificbiochemical reactionswhenenzymesandproteinsarebroughttogethertothesamespatiallocation.Similar spatial organizing principles are involved in genome regulation, where the 3D structure of the genomeappearstoplayaregulatoryfunctionbypositioninggenesinproximitytoremoteDNA regulatorysitesortolocalizedproteins.Again,physicalproximityisthoughttopromotespecific biochemical processes in gene regulation. While there is extensive evidence that spatial organizationisimportantforbiologicalfunction,welackaquantitativeframeworktounderstand howenzymeactivitiesandotherbiochemicalfunctionsareaffectedbyspatialorganization.This gapinourknowledgemustbeaddressedtounderstandfundamentalprocesseslikecellsignaling andgeneregulation,andtointervenetherapeuticallywhentheseprocessesaremisregulated.To address this challenge, I propose to develop new tools to systematically perturb structural organization both in cell signaling networks and in the genome. I plan to use these tools to understand the underlying mechanistic principles that enable cells to control biochemical reactionswithincrediblespatialandtemporalprecision.